环状RNA在皮肤相关疾病及创面愈合中的研究进展

环状RNA(circRNA)为一类具有连续共价闭环结构的新型非编码RNA(ncRNA),无3′及5′游离末端。其可作为微小RNA(miRNA)"分子海绵"调节转录或剪接,也可与RNA结合蛋白相互作用,在机体生理和病理过程中都起着关键作用。近来有研究表明,在与创面愈合相关的细胞(血管内皮细胞、角质细胞)增殖、迁移等活动中,有circRNA参与其中。本文回顾了circRNA在不同类型皮肤细胞中发挥的调节作用及其与皮肤相关疾病如皮肤鳞状细胞癌、基底细胞癌、重度痤疮的联系,旨在为阐释创面愈合的细胞分子机制提供新思路,以期为解决临床上创面治疗难题开拓新方向。     

细胞因子与胚胎皮肤无瘢痕愈合

从1971年Burrington首次发现孕中期的羊胎皮肤创伤后没有瘢痕形成,而妊娠晚期和出生后机体皮肤创伤后伤口愈合常为有瘢痕愈合的现象,并确立了“无瘢痕愈合”（Scarless Healing）的概念以来,这一概念就用于描述哺乳动物胚胎创伤愈合后不留瘢痕的特殊现象。有实验表明无瘢痕愈合是胚胎皮肤固有的特性。因此,学者们试图通过对胚胎的创伤愈合研究,了解无瘢痕愈合机制,而这一变化的内在机制目前仍不十分清楚,至今几乎所有的无瘢痕愈合现象还只在胎儿身上发现。以往的研究表明,皮肤无菌、湿润和低氧的生长环境对皮肤创面的修复结局影响较小,而胎儿皮肤伤口处的细胞因子的浓度变化密切相关。     

成纤维细胞及其相关因素在无瘢痕愈合中的研究进展

胎儿皮肤创伤后的无瘢痕愈合是人们追求的理想愈合模式。胚胎早期皮肤创伤后愈合迅速且无瘢痕形成,揭示胎儿无瘢痕愈合机制以提高创面修复愈合质量,对临床上瘢痕的防治具有非常重要的意义。近年来虽已做了大量研究,但对妊娠早期胎儿无瘢痕愈合的产生机制还不完全清楚,本文主要从胚胎成纤维细胞及其相关因素方面介绍其无瘢痕愈合的可能机制。     

皮肤成纤维细胞在创面愈合中的研究进展

皮肤成纤维细胞是参与创面愈合的主要修复细胞,近年来其异质性及其与周围细胞间的通讯正逐渐引起重视.真皮成纤维细胞亚群主要包括乳头状成纤维细胞和网状成纤维细胞,对创面愈合发挥不同的作用.成纤维细胞通过自分泌和旁分泌信号分子与周围细胞之间相互作用构成创面微环境,影响创面愈合.慢性创面中的成纤维细胞表现出多种功能障碍.本文就成...     

异体脱细胞真皮基质对大鼠皮肤瘢痕形成的影响

目的了解异体脱细胞真皮基质（accelular dermal matrix,ADM）对SD大鼠皮肤切口愈合后瘢痕形成的影响。方法4％NaOH溶液消蚀脱细胞法制备ADM,选用SD大鼠56只,每只大鼠背部脊柱两侧共做两道平行切口,建立皮肤切口模型。按自身对照分为实验组及对照组,实验组：将修剪成的ADM（3cm×0.3cm×0．1cm）植入切口,丝线缝合切口;对照组则原位缝合。术后3天、5天、7天、14天、21天、28天、63天（每个时相点8只）处死大鼠,取切口皮肤组织做HE、Masson染色,进行生物组织学检测,RT-PCR方法检测各组切口中成纤维细胞内Ⅰ型前胶原mRNA的表达水平。结果术后实验组未见明显瘢痕组织,而对照组愈合后见明显线性瘢痕形成。镜下观察实验组切口中ADM逐渐被改建成自体组织,3天、5天、7天、14天及21天实验组中成纤维细胞数量较对照组减少（P〈0．05）;实验组切口中胶原的生成在各个时间点较对照组均减少,其中7天、14天、21天、28天及63天实验组切口中胶原的生成较对照组明显减少（P〈0．01）;RT-PCR检测组织中成纤维细胞内Ⅰ型前胶原mRNA相对表达量对照组（0．809±0．042）比实验组（0．540±0．026）增高。结论ADM能抑制切口中成纤维细胞的增生和胶原的过度分泌,减少瘢痕的形成。     

皮肤瘢痕物理治疗研究进展

目的:根据基础和临床两方面总结近年皮肤瘢痕的物理治疗进展,认识物理治疗在治疗中的应用情况,并对未来物理治疗的前景进行了展望.方法:应用计算机检索Medine1990-01/2007-12有关皮肤瘢痕方面的文献,检索词"keloid,hypertrophic sear,treatment,keloid fibroblasts in vitro",限定文章语种为English.同时计算机检索中国期刊网全文数据库1990-01/2008-12相关皮肤瘢痕基础研究和治疗的文章,检索词"皮肤瘢痕、瘢痕疙瘩,增生性瘢痕,物理治疗",限定文章语种为中文.对资料进行初审,选取包括皮肤瘢痕的相关文献,开始查找全文.将与皮肤瘢痕基础研究和物理治疗有关的文献纳入标准.排除文献中重复研究,综述类文章.共检索到关于皮肤瘢痕的文献206篇,13篇资料提炼纳入标准.文章根据皮肤瘢痕的特点从基础研究和物理治疗两方面对皮肤瘢痕的文章进行综合、概括和评价.也对未来物理治疗的前景进行了展望.结果:随着对皮肤瘢痕物理治疗的日益重视和深入研究,早期利用功能康复综合疗法、冷冻疗法、加压疗法、放射疗法、激光疗法等在临床治疗中取得一定的成效.结论:随着对皮肤瘢痕发病机制研究的进一步深入,各种新兴物理治疗手段的涌现和原有物理技术的不断发展,以及同生物工程技术等多种技术的结合应用,如基因技术与物理治疗相结合、药物治疗与物理治疗相结合、手术治疗和物理治疗相结合等,有望为皮肤瘢痕的治疗提供新的突破点.     

增生性瘢痕和瘢痕疙瘩的发病机制

增生性瘢痕和瘢痕疙瘩是烧伤或手术等创伤后创面异常愈合反应的结果，以过量的组织纤维化和胶原蛋白沉积为特征，是现代医学上仍未解决的难题。本文综述了增生性瘢痕与瘢痕疙瘩的组织病理学差别，Ⅰ，Ⅲ型胶原蛋白及其基因表达的改变以及ＴＧＦβ，ＩＬⅠ，ＰＤＧＦ 等多种细胞因子与瘢痕形成的关系     

干细胞对创面愈合作用的研究进展

各种创伤造成的皮肤缺损直接影响患者的生活质量，甚至危及生命，尽快闭合创面、恢复功能、最终达到外表美观是治疗的目的。皮肤创面愈合是一个生物合成、细胞迁移分化过程的完美结合，包括炎性反应、细胞增殖、血管再生及重塑几个阶段。近20年，随着细胞学及分子生物技术的突飞猛进，人们对创面修复及组织重建的研究也有了很大的进展。     

整合素在烧伤创面愈合中的作用研究进展

整合素家族为跨膜糖蛋白受体家族,其作用是介导细胞与细胞外基质之间的相互作用,参与细胞相互之间的黏附功能。整合素通过双向信号转导,影响细胞的分化、增生与凋亡;整合素信号系统还可以通过调控细胞周期,产生细胞凋亡,影响瘢痕的形成。本文就整合素家族参与烧伤创面成纤维细胞分化、促进创面收缩,增强细胞外基质的收缩能力以及整合素连接激酶与创面愈合之间的关系作一综述。     

负压治疗促进皮肤创面愈合的研究进展

临床上,因急、慢性损伤导致的各种皮肤软组织缺损十分常见。创面治疗的基本措施是提供创面自行愈合的局部环境,或是通过外科干预直接封闭创面。适合创面愈合的理想的局部环境因素主要包括:湿润的、非感染的、具有丰富血供和均衡炎性调节因子的环境。负压治疗又称为负压创面疗法、负压封闭治疗,目前,负压治疗已成为创面处理领域重要的治疗手段之一,为很多复杂皮肤创面的处理提供了一个较为便捷、有效的方法。     

Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds

Skin regeneration remains a challenge, requiring a well-orchestrated interplay of cell–cell and cell–matrix signalling. Cell sheet (CS) engineering, which has the major advantage of allowing the retrieval of the intact cell layers along with their naturally organized extracellular matrix (ECM), has been poorly explored for the purpose of creating skin substitutes and skin regeneration. This work proposes the use of CS technology to engineer cellular constructs based on human keratinocytes (hKC), key players in wound re-epithelialization, dermal fibroblasts (hDFb), responsible for ECM remodelling, and dermal microvascular endothelial cells (hDMEC), part of the dermal vascular network and modulators of angiogenesis. Homotypic and heterotypic three-dimensional (3-D) CS-based constructs were developed simultaneously to target wound re-vascularization and re-epithelialization. After implantation of the constructs in murine full-thickness wounds, human cells were engrafted into the host wound bed and were present in the neotissue formed up to 14 days post-implantation. Different outcomes were obtained by varying the composition and organization of the 3-D constructs. Both hKC and hDMEC significantly contributed to re-epithelialization by promoting rapid wound closure and early epithelial coverage. Moreover, a significant increase in the density of vessels at day 7 and the incorporation of hDMEC in the neoformed vasculature confirmed its role over neotissue vacularization. As a whole, the obtained results confirmed that the proposed 3-D CS-based constructs provided the necessary cell machinery, when in a specific microenvironment, guiding both re-vascularization and re-epithelialization. Although dependent on the nature of the constructs, the results obtained sustain the hypothesis that different CS-based constructs lead to improved skin healing.     

Selected elements of extracellular matrix of the skin in diabetes and insulin resistance

PurposeReconstruction of the skin extracellular matrix is a physiological phenomenon occurring on a continuous basis. The aim of this study is to evaluate the content of basic enzymes preventing oxidative stress: superoxide dismutase 2 and 3 as well as catalase, the content of hyaluronic acid, and the activity of N-acetyl-β-d-hexosaminidase and β-d-glucuronidase in the skin of rats used as animal models of diabetes and insulin resistance, before and after the treatment.Materials and methodsThe study was conducted on a group of sexually mature male Wistar rats divided into 7 groups of 10 animals. Insulin resistance was induced by feeding the rats with a high-fat diet, and diabetes was induced by a single injection of streptozotocin. Chosen groups of rats were treated with insulin or metformin. After 8 weeks, we excised a fragment of shaved dorsal skin from anesthetized rats in each group.ResultsIn the course of diabetes and insulin resistance, an intensified defensive activity of cells against the oxidative stress was observed in the undamaged skin, expressed by an increase in the relative content of superoxide dismutase 2 and 3, catalase and the activity of N-acetyl-β-d-hexosaminidase and β-d-glucuronidase. Diabetes and insulin resistance cause similar skin damage, as there are no differences in the relative contents or specific activities of the examined parameters.ConclusionsInsulin and metformin improve the quality of the skin in rats with diabetes and insulin resistance, by restoring the content of hyaluronic acid to the healthy skin level.     

小肠黏膜下基质修复大鼠皮肤缺损的实验研究

目的制备脱细胞小肠黏膜下基质,修补全层皮肤缺损,为组织工程皮肤的体外构建提供实验依据。方法制备小肠黏膜下层,用Wistar大鼠建立全层皮肤缺损的创伤模型,分成小肠黏膜下层组,络合碘凡士林纱条组以及空白对照组,于手术后分阶段取材,宏观观察及组织学观察以上3组大鼠愈合过程。结果肠黏膜下层贴附皮肤不引起排斥反应,无伤口感染,小肠黏膜下层组在愈合速度方面快于络合碘凡士林纱条,空白对照组最慢。小肠黏膜下层组愈合无瘢痕,皮肤附件生长良好,而其余两组瘢痕愈合,皮肤附件仅生长于伤口边缘处。结论小肠黏膜下基质的生物相容性良好,可以作为组织工程皮肤的细胞支架。     

医用皮肤减张闭合器在胸骨切开术后裂开手术治疗中的应用效果

目的 探讨医用皮肤减张闭合器在胸骨切开术后裂开手术治疗中的作用.方法 选取空军军医大学第一附属医院烧伤与皮肤外科于2017年1月至2020年6月收治的胸骨切开术后裂开患者24例,按随机数字表法将患者分为联合治疗组(n = 12)和常规治疗组(n = 12).2组患者均在彻底清创的基础上,根据感染创面的位置、血供及感染程...     

血管内皮生长因子基因感染对大鼠创面移植复合皮的影响

目的观察血管内皮生长因子（VEGF）基因感染的复合皮移植大鼠创面后的愈合效果。方法培养自体表皮细胞和异体成纤维细胞，用腺病毒介导的血管内皮生长因子（Ad-VEGF）感染大鼠成纤维细胞。分别构建感染的复合皮（自体表皮细胞＋人脱细胞真皮基质＋Ad-VEGF基因感染的成纤维细胞）和未感染的复合皮（自体表皮细胞＋人脱细胞真皮基质＋未感染的成纤维细胞），移植于大鼠背部皮肤缺损创面。术后2周观察大鼠创面移植皮片存活情况。术后2、4、6周观察大鼠复合皮大体情况，并取创面组织标本进行组织学观察。结果（1）术后2周，感染组复合皮成活面积大于未感染组复合皮成活面积；（2）术后2周，未感染组创面部分结痂。术后6周感染组复合皮表面光滑，有弹性，抗摩擦性强，愈合效果优于未感染组；（3）术后2周感染组皮片内可见较多的毛细血管分布；6周时表皮细胞分化达5-7层，纤维排列致密整齐，毛细血管分布均匀。结论用Ad-VEGF基因感染复合皮，可以刺激新生血管形成，明显提高皮片愈合质量。     

Molecular aspects of skin ageing

Ageing of human skin may result from both the passage of time (intrinsic ageing) and from cumulative exposure to external influences (extrinsic ageing) such as ultraviolet radiation (UVR) which promote wrinkle formation and loss of tissue elasticity. Whilst both ageing processes are associated with phenotypic changes in cutaneous cells, the major functional manifestations of ageing occur as a consequence of structural and compositional remodeling of normally long-lived dermal extracellular matrix proteins. This review briefly considers the effects of ageing on dermal collagens and proteoglycans before focusing on the mechanisms, functional consequences and treatment of elastic fibre remodeling in ageing skin. The early stages of photoageing are characterised by the differential degradation of elastic fibre proteins and whilst the activity of extracellular matrix proteases is increased in photoexposed skin, the substrate specificity of these enzymes is low. We have recently shown however, that isolated fibrillin microfibrils are susceptible to direct degradation by physiologically attainable doses of UV-B radiation and that elastic fibre proteins as a group are highly enriched in UV-absorbing amino acid residues. Functionally, elastic fibre remodeling events may adversely impact on: the mechanical properties of tissues, the recruitment and activation of immune cells, the expression of matrix metalloproteinases and cytokine signaling (by perturbing fibrillin microfibril sequestration of TGFβ). Finally, newly developed topical interventions appear to be capable of regenerating elements of the elastic fibre system in ageing skin, whilst systemic treatments may potentially prevent the pathological tissue remodeling events which occur in response to elastic fibre degradation.